Non-small cell lung cancer (NSCLC) is the dominant form of human lung cancer, representing almost 80% of the cancers in lung cancer patients. It usually grows and spreads more slowly than small cell lung cancer. There are three forms of NSCLC: adenocarcinomas are often found in an outer area of the lung; squamous cell carcinomas are usually found in the center of the lung by an air tube (bronchus), and large cell carcinomas can occur in any part of the lung. Large cell carcinomas tend to grow and spread faster than the other two types. Smoking causes most cases of lung cancer. Being around the smoke from others (secondhand smoke) also raises the risk for lung cancer. High levels of air pollution, working with or near cancer-causing chemicals or materials, and drinking water containing certain contaminants such as arsenic can increase the risk for lung cancer. Radiation therapy to the lungs can also increase the risk. Prognosis and selection of therapy for NSCLC are influenced by the stage of the cancer, the age of the patient, pathologic characteristics of the primary tumor, race and by general health. Three major treatments for cancer are surgery, radiation, and drug therapy. No treatment fits every patient, and often two or more treatments are required.
Various genes have been associated with an increased susceptibility to cancer. Evaluation of gene expression (e.g., stability of RNA and quantitation of expression) is refined and extended by measuring methylation profiles of CpG-containing sequences. Regions of unusually high GC content have been described in many genes and may be referred to as “CpG islands”. The cytosine of CpG islands can be modified by methyltransferase to produce a methylated derivative: 5-methylcytosine (5me-C). If a methylated cytosine is located in the promoter region of a gene, the gene is likely to be silenced.
Tumor-specific changes in DNA methylation have been observed in many different malignancies and are frequently described as global hypomethylation combined with local hypermethylation. Global hypomethylation is linked to genomic instability of a tumor, whereas hypermethylation of specific genes correlates with their silencing and can induce point mutations owing to spontaneous deamination of 5me-C (transversion C>T). Silencing of a tumor suppressor gene can lead to enhanced transformation and increased tumor growth through disruption of the normal regulatory mechanisms of the affected cell.